Normal and Neoplastic Stem Cells

1. Benson M. George1,2,3,5,
2. Kevin S. Kao1,2,
3. Kristopher D. Marjon1,2,3,
4. Tal Raveh1 and
5. Irving L. Weissman1,2,3,4

1. ¹Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305
2. ²Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, Stanford, California 94305
3. ³Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California 94305
4. ⁴Department of Pathology, Stanford University Medical Center, Stanford, California 94305

1. Correspondence: irv{at}stanford.edu

1. ↵5 These authors contributed equally to this work.

Abstract

A stem cell is broadly defined as a cell that retains the capacity to self-renew, a feature that confers the ability to continuously make identical daughter cells or additional cells that will differentiate into downstream progeny. This highly regulated genetic program to retain “stemness” is under active investigation. Research in our laboratory has explored similarities and differences in embryonic, tissue-specific, and neoplastic stem cells and their terminally differentiated counterparts. In this review, we will focus on the contributions of our laboratory, in particular on the studies that identified the mouse hematopoietic stem cell (HSC) and the human leukemic stem cell. These studies have led to significant improvements in both preclinical and clinical research, including improved clinical bone marrow transplantation protocols, isolation of nonleukemic HSCs, a cancer immunotherapy currently in clinical trials, and development of a HSC reporter mouse. These studies and the current follow-up research by us and others will continue to identify the properties, function, and regulation of both normal and neoplastic stem cells.